Injection Vaccines Formulated with Nucleotide, Liposomal or Mineral Oil Adjuvants Induce Distinct Differences in Immunogenicity in Rainbow Trout

Abstract

Protection facilitated by the widespread use of mineral oil adjuvanted injection vaccines in salmonid fish comes with adverse effects of varying severity. In this study, we characterized the immunological profiles of two alternative vaccine formulations, both with proven efficacy and an improved safety profile in rainbow trout. Experimental injection vaccines were prepared on an identical whole-cell Aeromonas salmonicida bacterin platform and were formulated with CpG oligodeoxynucleotides, a liposomal (CAF01) or a benchmark mineral oil adjuvant, respectively. A naïve group, as well as bacterin and saline-injected groups were also included. Following administration, antigen-specific serum antibody titers, the tissue distribution of immune cell markers, and the expression of immune-relevant genes following the in vitro antigenic restimulation of anterior kidney leukocytes was investigated. Immunohistochemical staining suggested prolonged antigen presentation for the particulate formulations and increased mucosal presence of antigen-presenting cells in all immunized fish. Unlike the other immunized groups, the CAF01 group only displayed a transient elevation in specific antibody titers and immunohistochemical observations, and the transcription data suggest an increased role of cell-mediated immunity for this group. Finally, the transcription profile of the CpG formulation approached that of a TH1 profile. When compared to the benchmark formulation, CAF01 and CpG adjuvants induce slight, but distinct differences in the resulting protective immune responses. This is important, as it allows a broader immunological approach for the future development of safer vaccines.

Pulmonary Administration of the Liposome-Based Adjuvant CAF01: Effect of Surface Charge on Mucosal Adjuvant Function

“…We observed a variability in the H56-specific T cell responses and the numbers of GC B cells and T FH cells, especially among CAF01 and 75:25:0 formulations. In general, we do see a rather high variability with these types of adjuvants. − The variability might be related to the mechanism of action: upon injection, the vaccine forms a depot at the site of injection upon interaction with proteins, and it is not possible to fully control this depot formation. In addition, the liposome formulations are not fully monodisperse.…”

Advancements in Fish Vaccination: Current Innovations and Future Horizons in Aquaculture Health Management

“…However, this form of vaccination induces adverse reactions, including internal lesions and reduction in weight [81]. There is an emphasis on identifying what can be done to reduce the severity of these reactions, and on developing safer, yet effective vaccines [84][85][86]. Live attenuated vaccines containing A-layer and O-deficient strains of Aeromonas salmonicida have been shown to confer significant protection, and there are researchers looking into recombinant vaccines for other species impacted by the disease, including rainbow trout [67,[87][88][89].…”

C-Type Lectins in Veterinary Species: Recent Advancements and Applications

“…Similarly, a TDB-based experimental liposomal vaccine adjuvant, CAF01, was shown to mediate long-lived M. tuberculosis -specific T-cell responses in humans [ 109 ] and enhanced the efficacy of a commercially available inactivated influenza vaccine in ferret models [ 110 ]. This adjuvant system was also used for rainbow trout immunization against Aeromonas salmonicida and induced enhanced cellular immunity in comparison to formulation with the standard adjuvant mineral oil [ 111 ]. Further trehalose-based CTL-targeting compounds, such as the 2-hydroxy benzoic acid coupled trehalose compound 6,6′-bis-(3,5-di-tert-butylsalisate)-α,α-trehalose (UM1024), demonstrated high Mincle targeting specificity and low cytotoxicity in mouse and human peripheral blood mononuclear cells (PBMCs) in vitro and robust immunogenicity in a mouse model [ 112 ].…”